[Methotrexate in therapy of gastrointestinal diseases]

This review is not only a comprehensive synopsis of the published data on methotrexate treatment for inflammatory bowel disease and primary biliary cirrhosis but gives also an overview about acting mechanisms, pharmacologic properties and limiting toxicities of low-dose methotrexate. Methotrexate and its polyglutamate analogues are structurally related to folic acid and inhibit many enzymes in the metabolic pathway of folic acid. Long-term low-dose methotrexate treatment (7.5-25 mg) inhibits production of thymidylate, purines, and methionine and leads to intracellulary accumulation of adenosin. These actions lead to inhibition of cellular proliferation, decreased formation of antibodies and reduced productions of inflammatory medicators. Several trials have demonstrated the efficacy of low-dose methotrexate therapy for certain indications as a promising new agent in the treatment of inflammatory bowel disease and primary biliary cirrhosis. However, several serious toxicities potentially limit its use.